Topic:Cytokines
Cytokines are small proteins that are important in cell signaling and are produced by various cell types in horses, particularly during immune responses. These molecules facilitate communication between cells and play a role in regulating inflammation, immune function, and hematopoiesis. In horses, cytokines are involved in numerous physiological and pathological processes, including infection, inflammation, and wound healing. Examples of cytokines studied in equine research include interleukins, interferons, and tumor necrosis factors. Their expression levels can change in response to disease states, making them potential biomarkers for assessing equine health and disease progression. This page compiles peer-reviewed research studies and scholarly articles that explore the role, regulation, and clinical implications of cytokines in equine health.
Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career. Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disea...
Autologous Conditioned Serum. Autologous conditioned serum was developed in the mid 1990s as an expeditious, practical, and relatively inexpensive means of generating the interleukin-1 receptor antagonist, a naturally occurring inhibitor of the cytokine interleukin-1. The latter is thought to be an important mediator of inflammation, pain, and tissue destruction in musculoskeletal conditions. ACS has been widely and successfully used in the local treatment of human and equine osteoarthritis and radicular compression; it has also shown promise in treating tendinopathies, muscle injuries, and tunnel widening after reconstruc...
Immune-modulating properties of horse milk administered to mice sensitized to cow milk. The aim of this study was to examine immune adaptive changes, the expression of innate biomarkers and variations in intestinal microbiota composition after horse-milk administration in BALB/c mice, which were sensitized intraperitoneally using cow β-lactoglobulin and α-casein with aluminum adjuvant. We measured serum antibody IgE levels and the expression of MCP-1, IL-4, and TNF-α in duodenal samples. Changes in immune cell populations in peripheral blood were quantified using flow cytometry, and intestinal microbiota composition was assessed using real-time PCR. We found that horse-milk ad...
The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating-induced endometritis. In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six ma...
Expression of T helper cell-associated inflammatory mediator mRNAs in cells of bronchoalveolar lavage fluid samples and oxygen concentration in arterial blood samples from healthy horses exposed to hyperbaric oxygen. OBJECTIVE To evaluate the mRNA expression of T helper (Th)1, Th2, and Th17 cell-associated inflammatory mediators in cells of bronchoalveolar lavage fluid samples collected from healthy horses exposed to hyperbaric oxygen (HBO) and to monitor blood oxygen concentration during and following HBO therapy. ANIMALS 8 healthy horses. PROCEDURES In a randomized controlled crossover design study, each horse was exposed (beginning day 1) to 100% oxygen at a maximum of 3 atmospheres absolute (304 kPa) daily for 10 days or ambient air at atmospheric pressure in the HBO chamber for an equivalent amount of...
Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis. To determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes. Methods: Twenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease. Methods: Samples of AH and serum were obtained from horses wit...
Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation. Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lu...
Identification of SP110 in horse (Equus caballus): Isolation of novel splice variants and evidence of activation effects on macrophages. SP110 has previously shown to be a genetic determinant of host resistance to the intracellular pathogen infection in mouse and human. However, its relevant biological information in large non-primate animals still remains unknown. Here we report the novel discovery and characterization of three transcript variants of horse SP110. The transcript variant 1 (Tv1) of horse SP110 with the longest open reading frame has four domains (Sp100, SAND, PHD and Bromo domain). Tv2 and Tv3 share the same N-terminal sequence as Tv1, which contains Sp100 and SAND. We show that Tv2 is generated from alternative...
The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis? Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1) has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translatio...
Orf virus interleukin-10 and vascular endothelial growth factor-E modulate gene expression in cultured equine dermal fibroblasts. Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. Objective: The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression an...
Gingival Toll-like receptor and cytokine messenger RNA levels in equine periodontitis and oral health. Equine periodontitis is a common and painful condition. However, the disease often goes unnoticed by owners and is thus a major welfare concern. The aetiopathogenesis of the condition remains poorly understood and has been investigated in few studies. The innate immune system is known to play an important role in human periodontitis, but its role in equine periodontitis has not been examined. Objective: To quantify the messenger (m)RNA levels of Toll-like receptors (TLRs) and cytokines in gingival tissue from orally healthy horses and those affected by periodontitis. Methods: Observational stu...
Intratracheal therapy with autologous bone marrow-derived mononuclear cells reduces airway inflammation in horses with recurrent airway obstruction. This research evaluated the effects of bone marrow-derived mononuclear cells (BMMCs) on the inflammatory process in the equine recurrent airway obstruction (RAO). Eight horses in RAO clinical score were divided into cell therapy group (Gcel) treated with a single intratracheal dose of BMMCs, and dexamethasone group (Gdex) treated with 21days of oral dexamethasone. The horses were clinically revaluated on days 7 and 21, together with cytological evaluation of the BALF, and detection of inflammatory markers (interleukins [IL]-10, -4, and -17, and interferon γ and α). There were decreases in re...
Immunological and pathological investigations in equine experimental uveitis. The pathogenic mechanism of equine recurrent uveitis (ERU) is still poorly defined and many variations between experimental animal models and spontaneous disease exist. Objective: The aim of our study was to investigate if Th17 cell-mediated response plays role in the pathogenesis of the used experimental model in horses and to reveal its pathological findings. Methods: Experimental uveitis was induced in 6 healthy horses. The concentrations of retinal autoantigen CRALBP and IL-17 were measured using ELISA in aqueous humor and vitreous body of the 12 inflamed eyes as well as in 12 control non-...
Release kinetics of tumor necrosis factor-α and interleukin-1 receptor antagonist in the equine whole blood. Horses are much predisposed and susceptible to excessive and acute inflammatory responses that cause the recruitment and stimulation of polymorphnuclear granulocytes (PMN) together with peripheral blood mononuclear cells (PBMC) and the release of cytokines. The aim of the study is to develop easy, quick, cheap and reproducible methods for measuring tumor necrosis factor alpha (TNF-α) and interleukin-1 receptor antagonist (IL-1Ra) in the equine whole blood cultures ex-vivo time- and concentration-dependently. Results: Horse whole blood diluted to 10, 20 and 50 % was stimulated with lipopolysa...
Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments. Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow ...
Enhanced cytotoxicity of bleomycin, cisplatin, and carboplatin on equine sarcoid cells following electroporation-mediated delivery in vitro. Electroporation is a method used to deliver poorly permeant chemotherapeutic drugs to tumor cells, potentiating the cytotoxic effects of drugs and overall clinical response. Despite existing evidence of the potential benefits of electroporation to enhance the antitumoral effects of drugs, there is a lack of understanding about the effects of electroporation on equine tumor cells. This study investigated the combined effects of electroporation and bleomycin, cisplatin, and carboplatin on an equine sarcoid cell line (EqS04b). The use of electroporation increases the cytotoxic effects of bleomyci...
Inflammation-induced transgene expression in genetically engineered equine mesenchymal stem cells. Osteoarthritis, a chronic and progressive degenerative joint disorder, ranks amongst the top five causes of disability. Given the high incidence, associated socioeconomic costs and the absence of effective disease-modifying therapies of osteoarthritis, cell-based treatments offer a promising new approach. Owing to their paracrine, differentiation and self-renewal abilities, mesenchymal stem cells (MSCs) have great potential for regenerative medicine, which might be further enhanced by targeted gene therapy. Hence, the development of systems allowing transgene expression, particularly when regu...
Effects of pro-inflammatory cytokines on chondrogenesis of equine mesenchymal stromal cells derived from bone marrow or synovial fluid. Mesenchymal stromal cells (MSCs) have the capacity to differentiate into cells of mesenchymal lineage, such as chondrocytes, and have potential for use in regeneration of equine articular cartilage. MSCs instilled intra-articularly would be exposed to the inflamed environment associated with equine osteoarthritis (OA), which may compromise their function and ability to heal a cartilaginous defect. The aim of this study was to assess the ability of equine adult MSCs to differentiate into chondrocytes when stimulated with pro-inflammatory cytokines. MSCs derived from equine bone marrow (BM) and ...
Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment. Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses ...
Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares. Mares that fail to conceive or lose their embryos, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). In this study, the question was addressed: does SE fully activate selected mechanisms of innate immunity in mares? For this aim, expression of mRNAs for Toll-like Receptor 2 and 4 (TLR 2/4), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF) was examined in control mares versus either mares suffering from chronic endometritis (ChE) or subacute suppurative endometritis (SSE). The concentrations of IL-1β, ...
The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids. Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. To determine whether IL-17 dire...
Effects of polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxypterostilbene on lymphocyte pro-inflammatory cytokine production of senior horses in vitro. Senior horses (aged ≥ 20 years) exhibit increased chronic, low-grade inflammation systemically, termed inflamm-aging. Inflammation is associated with many afflictions common to the horse, including laminitis and osteoarthritis, which are commonly treated with the non-steroidal anti-inflammatory drugs (NSAIDs) flunixin meglumine and phenylbutazone. Although these NSAIDs are effective in treating acute inflammatory problems, long-term treatment with NSAIDs can result in negative side effects. Thus, bioactive polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxy...
Duration of in vivo endotoxin tolerance in horses. Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin toler...
An Adenoviral Vector Based Vaccine for Rhodococcus equi. Rhodococcus equi is a respiratory pathogen which primarily infects foals and is endemic on farms around the world with 50% mortality and 80% morbidity in affected foals. Unless detected early and treated appropriately the disease can be fatal. Currently, there is no vaccine available to prevent this disease. For decades researchers have endeavoured to develop an effective vaccine to no avail. In this study a novel human adenoviral vector vaccine for R. equi was developed and tested in the mouse model. This vaccine generated a strong antibody and cytokine response and clearance of R. equi was d...
Wound-healing markers after autologous and allogeneic epithelial-like stem cell treatment. Several cytokines and growth factors play an essential role in skin regeneration and epithelial-like stem cells (EpSCs) have beneficial effects on wound healing in horses. However, there are no reports available on the expression of these growth factors and cytokines after EpSC therapy. Methods: Wounds of 6 cm(2) were induced in the gluteus region of 6 horses and treated with (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Real time polymerase chain reaction was performed on tissue biopsies taken 1 and 5 weeks after these treatments to evaluate...
Cathepsin K inhibition renders equine bone marrow nucleated cells hypo-responsive to LPS and unmethylated CpG stimulation in vitro. Cathepsin K (CatK) is an important enzyme regulating bone degradation and has been shown to contribute to the immune response. We have studied two inflammatory models in equine bone marrow nucleated cells (BMNCs); the LPS and the unmethylated CpG stimulation with the following objectives to: 1.determine whether CatK inhibition will alter the cytokine secretion by stimulated BMNCs; specifically IL-1β, IL-6, and TNF-α, and 2.determine the changes in BMNCs surface markers' expression and MHC II molecule under CatK inhibition. Cathepsin K inhibition promoted BMNCs viability and reduced cell apop...
Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties. Mesenchymal stem cells (MSCs) are being investigated for the treatment of equine joint diseases because of their regenerative potential. Recently, the focus mainly has addressed to their immunomodulatory capacities. Inflammation plays a central role in joint pathologies, since the release of proinflammatory mediators to the synovial fluid (SF) leads to the activation of enzymatic degradation of the cartilage. MSCs can modulate the local immune environment through direct or paracrine interaction with immune cells, suppressing their proliferation and re-addressing their functions. Proinflammator...
Our current understanding of the pathophysiology of equine endometritis with an emphasis on breeding-induced endometritis. Equine endometritis is characterized by the expression of pro- and anti- inflammatory cytokines and an influx of polymorphonuclear neutrophils (PMNs) into the uterus. Mares resistant to persistent endometritis clear the inflammation within 24-36 h after exposure to microorganisms or semen. These mares have a rapid increase of pro-inflammatory cytokines and an upregulation of inflammatory modulating cytokines within 6h after exposure to inflammatory challenge. In conjunction with effective uterine contractions, these events are believed to be responsible for the transient nature of the inflamma...
Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. The live equine infectious anemia virus (EIAV) vaccine strain EIAVDLV121 was developed by in vitro attenuation of a virulent strain, EIAVLN40, in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural EIAV infection conditions. The detailed biological features of this attenuated virus remain to be further investigated. Experimental inoculation with EIAVDLV121 did not result in clinical symptoms even with immunosuppressive treatment in our previous studies. Here, we further investigated whether the replication of the vaccine strain EIAVDLV121 in exper...
Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses. The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercis...